Age-Related Blood Levels of Creatine Kinase-MM in Newborns and Patients with Duchenne Muscular Dystrophy: Considerations for the Development of Newborn Screening Algorithms.

Duchenne muscular dystrophy (DMD) is an X-linked progressive disorder and the most common type of muscular dystrophy in children. As newborn screening (NBS) for DMD undergoes evaluation for the Recommended Uniform Screening Panel and is already mandated in multiple states, refining NBS algorithms is of utmost importance. NBS for DMD involves measuring creatine kinase-MM (CK-MM) concentration-a biomarker of muscle damage-in dried blood spots. The current test is FDA-approved for samples obtained less than 72 h after birth. Separate reference ranges are needed for samples collected later than 72 h after birth. In this study, we investigated the relationship between age and CK-MM in presumed healthy newborns to inform NBS algorithm designs. In patients with DMD, CK-MM is persistently elevated in childhood and adolescence, while it may be transiently elevated for other reasons in healthy newborns. CK-MM decrease over time was demonstrated by a population sample of 20,306 presumed healthy newborns tested between 0 and 60 days of life and repeat testing of 53 newborns on two separate days. In the population sample, CK-MM concentration was highest in the second 12 h period of life (median = 318 ng/mL) when only 57.6% of newborns tested below 360 ng/mL, the lowest previously published cutoff. By 72 h of age, median CK-MM concentration was 97 ng/mL, and 96.0% of infants had concentrations below 360 ng/mL. Between 72 h and 60 days, median CK-MM concentration ranged from 32 to 37 ng/mL. Establishing age-related cutoffs is crucial for optimizing the sensitivity and specificity of NBS for DMD.

Facilitators and Barriers to Adherence to Anti-Retroviral Treatment Among Pregnant or Breastfeeding Women Living with HIV and Perinatally Infected Infants: A Scoping Review.

In 2022, 54% of 1.5 million children (age 0-14) living with HIV had access to anti-retroviral medication (ART). Adherence to ART for pregnant or breastfeeding HIV + women is critical for maintaining their personal health and to prevent mother-to-child-transmission (MTCT). For HIV + infants, adherence is essential to establish early viremic control and is contingent on caregiver administration. We conducted a scoping review to systematically identify and categorize the influences on ART adherence for pregnant or breastfeeding HIV + women and their HIV + infants. We searched databases in June 2023 and employed the Social-Ecological Model (SEM) to organize facilitators and barriers to adherence referenced in published articles. All articles published before 2016 were excluded due to updated guidelines from WHO on MTCT and ART. Our analysis included 52 articles. 50/52 took place in Africa and used cross-sectional and mixed-methods design. Barriers to adherence for pregnant or breastfeeding HIV + women included maternal education, self-efficacy, social support, and social/economic context. Barriers to infant adherence included development, nutrition, age of treatment initiation, disclosure, and ART side effects. Additional facilitators and barriers to adherence are presented at family, extra-familial, and socio-cultural SEM levels. Stigma was the most salient barrier referenced across the entire continuum of HIV care and all SEM levels. This review revealed a dearth of literature focusing on HIV + infants who are dependent on their caregivers for ART adherence and lack of a standard adherence measure. We identified multi-leveled influences on adherence impacting both the mother and infant and are amenable to public health intervention.

Return of participant-level clinical trial results to participants: pilot of a simplified centralised approach.

OBJECTIVES: Public access databases such as clinicaltrials.gov achieve dissemination of clinical trial design and aggregated study results. However, return of participant-level data is rarely done. A key barrier includes the proprietary ownership of data by the sponsor. Additionally, investigators may not have access to centralised data, and per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice, must maintain the confidentiality of participants. This study piloted an approach to return both individual and aggregate clinical trial data to parents of children participating in a series of open-label clinical trials. SETTING AND DESIGN: A small biotech company obtained central ethics approval (centralised institutional review board [IRB], non-exempt). The study was advertised via parent advocacy groups. Parents of trial participants were offered the option to contact an employee (coordinator) within the company, requesting return of their child's study results. Ethics approval covered participation in six countries. The study focused on the sequential clinical trials of vamorolone VBP15-002 (NCT02760264) and VBP15-003 (NCT02760277) (post-results). INTERVENTIONS: Contact initiated by the parent enabled the coordinator to obtain informed consent (and separate General Data Protection Regulations consent), with phone translation when needed. Using date of birth and study site location provided by the parent, the data manager reported the participant number to the coordinator. The coordinator retrieved and compiled data, along with an aggregate summary, which was mailed via a password protected and encrypted memory device to the parent. Prereturn and postreturn surveys were sent to consented parents (n=19; 40% of 48 total trial participants) and investigators. RESULTS: Prereturn surveys indicated a request for as much data as offered, in all formats offered. Postreturn survey showed high satisfaction with the process and data returned. Survey of the physician site investigators (n=10; 100% participation of investigators) voiced general satisfaction with the process, with some reservations. CONCLUSIONS: This pilot study demonstrates an innovative, cost-effective, centralised and labour conservative approach to return of participant-level and aggregate data to participants in studies.

Parent perspectives following newborn screening resulting in diagnoses of fragile X syndrome or fragile X premutation.

BACKGROUND: Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. Early Check, a voluntary newborn screening study, screened 18,833 newborns for FXS over ∼3 years. Exploring parental attitudes and perspectives can provide insight to the potential future acceptability of public health screening. METHODS AND PROCEDURES: Mothers of infants who received a screen positive result for FXS (n = 6) or fragile X premutation (FXPM; n = 18) were interviewed about their perceptions and experiences. OUTCOMES AND RESULTS: Mothers of children with FXS described utility in receiving information about their child, particularly to monitor for potential developmental issues and intervene early; overall mothers did not regret participating. Mothers reported various reactions to receiving the FXS or FXPM results including (1) stress and worry; (2) guilt; (3) sadness and disappointment; (4) neutrality, relief, and acceptance; and (5) confusion and uncertainty. CONCLUSIONS AND IMPLICATIONS: Despite initial reactions such as sadness, stress, and worry, mothers found value in learning of their child's presymptomatic diagnosis of FXS, particularly the anticipated long-term benefits of early diagnosis to their child's health and wellbeing. Our results indicate that professionals returning positive newborn screening results should anticipate and prepare for reactions such as parental shock, guilt, sadness, and uncertainty. Genetic counseling and psychosocial support are critical to supporting families.

Role Preferences in Medical Decision Making: Relevance and Implications for Health Preference Research.

Health preference research (HPR) is being increasingly conducted to better understand patient preferences for medical decisions. However, patients vary in their desire to play an active role in medical decisions. Until now, few studies have considered patients' preferred roles in decision making. In this opinion paper, we advocate for HPR researchers to assess and account for role preferences in their studies, to increase the relevance of their work for medical and shared decision making. We provide recommendations on how role preferences can be elicited and integrated with health preferences: (1) in formative research prior to a health preference study that aims to inform medical decisions or decision makers, (2a) in the development of health preference instruments, for instance by incorporating a role preference instrument and (2b) by clarifying the respondent's role in the decision prior to the preference elicitation task or by including role preferences as an attribute in the task itself, and (3) in statistical analysis by including random parameters or latent classes to raise awareness of heterogeneity in role preferences and how it relates to health preferences. Finally, we suggest redefining the decision process as a model that integrates the role and health preferences of the different parties that are involved. We believe that the field of HPR would benefit from learning more about the extent to which role preferences relate to health preferences, within the context of medical and shared decision making.

Two years of newborn screening for Duchenne muscular dystrophy as a part of the statewide Early Check research program in North Carolina.

PURPOSE: Current and emerging treatments for Duchenne muscular dystrophy (DMD) position DMD as a candidate condition for newborn screening (NBS). In anticipation of the nomination of DMD for universal NBS, we conducted a prospective study under the Early Check voluntary NBS research program in North Carolina, United States. METHODS: We performed screening for creatine kinase-MM (CK-MM), a biomarker of muscle damage, on residual routine newborn dried blood spots (DBS) from participating newborns. Total creatine kinase testing and next generation sequencing of an 86-neuromuscular gene panel that included DMD were offered to parents of newborns who screened positive. Bivariate and multivariable analyses were performed to assess effects of biological and demographic predictors on CK-MM levels in DBS. RESULTS: We screened 13,354 newborns and identified 2 males with DMD. The provisional 1626 ng/mL cutoff was raised to 2032 ng/mL to improve specificity, and additional cutoffs (900 and 360 ng/mL) were implemented to improve sensitivity for older and low-birthweight newborns. CONCLUSION: Population-scale screening for elevated CK-MM in DBS is a feasible approach to identify newborns with DMD. Inclusion of birthweight- and age-specific cutoffs, repeat creatine kinase testing after 72 hours of age, and DMD sequencing improve sensitivity and specificity of screening.

Perceptions of Rapid Antiretroviral Therapy Initiation Among Participants of The Netherlands Cohort Study on Acute HIV Infection.

Starting antiretroviral therapy (ART) same-day, or as soon as possible after HIV diagnosis is advised in guidelines worldwide. Especially during acute HIV infection (AHI), rapid ART start may be more urgent because of a higher risk of transmission or symptoms of acute retroviral syndrome. During this phase, rapid ART start may have additional benefits for viral reservoir size and host immunity. We explored perceptions of rapid ART start among participants of The Netherlands Cohort Study on Acute HIV infection (NOVA study), who started ART rapidly after diagnosis of AHI. We conducted 20 in-depth qualitative interviews with NOVA study participants between October and December 2018. Data were analyzed thematically, using inductive and iterative coding techniques. Roughly half of the participants stated they felt well-informed about the importance of (rapid) ART. Starting ART rapidly was perceived positively by almost all participants, mostly because of the expected benefits on their health, and to prevent HIV transmission. Rapid ART start was seen as a way to cope with the diagnosis. However, a more negative perception was that rapid ART start confronted participants with their diagnosis, when they were still adjusting to a new situation. Our results show that among people diagnosed during AHI, rapid ART is well-accepted. These results should be encouraging to HIV care providers who encounter people with AHI in their clinical practice and to researchers who carry out cure-related studies, in which early ART is often included. The Clinical Trial Registration number is NCT05728996.

Corrigendum to "HIV remission trial investigators' attitudes towards risk and risk mitigation in trials that include treatment interruption" [J Virus Erad 9 (2) (June 2023) 100331].

[This corrects the article DOI: 10.1016/j.jve.2023.100331.].

HIV remission trial investigators' attitudes towards risk and risk mitigation in trials that include treatment interruption.

Early-phase HIV remission ("cure") trials aim to test interventions developed to eradicate HIV or to sustainably control HIV without antiretroviral treatment (ART). Many remission trials include analytic treatment interruption (ATI) to evaluate interventions, which increases the risk to participants and their sexual partners. We conducted an online questionnaire of international HIV remission trial investigators and other study team members to assess their expectations regarding the time to achieve long-term control of HIV replication without treatment (functional cure) or complete eradication of replication-competent HIV virus (sterilizing cure); attitudes toward HIV remission research and the feasibility, acceptability, and efficacy of six HIV transmission risk mitigation strategies during trials with ATI of fixed duration. Nearly half of respondents (47%) reported expecting a functional cure for HIV to be achieved in 5-10 years, and one-third (35%) reported 10-20 years for a sterilizing cure to be achieved. On a scale of -3 to 3, mean scores indicated greater respondent concern about the risk of HIV transmission to partners during ATI (Time to rebound Mean: 0.4 and Fixed duration Mean: 11), compared to participant health risks from ATI (Time to Rebound Mean: -.9 and Fixed duration Mean: 0.0). With regard to feasibility, acceptability, and efficacy respectively, mitigation efforts rated positively included: requiring counseling for potential participants (Means: 2.3; 2.1; and 1.1), providing partner referrals for PrEP (Means: 1.3; 1.3; 1.5), providing pre-exposure proxylaxis directly to partners (Means: 1.0; 1.5; 1.6), and monitoring participants for new sexually transmitted disease acquisition (Means: 1.9; 1.4; 1.0). Respondents were less positive about requiring that participants' sexual partner(s) participate in risk counseling or limiting participation to those who commit to abstaining from sex during the entire ATI period. Our study demonstrates that HIV remission trial investigators and study team members are concerned about the risk of transmission to sexual partners during ATI. Separating the assessment of risk mitigation strategies for transmission risk into feasibility, acceptability, and efficacy allows the discovery of strategies that may best achieve all three outcomes. Additional research is needed to compare these more fine-grained assessments with views held by other investigators, people living with HIV, and trial participants.

Defining critical educational components of informed consent for genetic testing: views of US-based genetic counselors and medical geneticists.

The Clinical Genome Resource (ClinGen) Consent and Disclosure Recommendation (CADRe) framework proposes that key components of informed consent for genetic testing can be covered with a targeted discussion for many conditions rather than a time-intensive traditional genetic counseling approach. We surveyed US genetics professionals (medical geneticists and genetic counselors) on their response to scenarios that proposed core informed consent concepts for clinical genetic testing developed in a prior expert consensus process. The anonymous online survey included responses to 3 (of 6 possible) different clinical scenarios that summarized the application of the core concepts. There was a binary (yes/no) question asking respondents whether they agreed the scenarios included the minimum necessary and critical educational concepts to allow an informed decision. Respondents then provided open-ended feedback on what concepts were missing or could be removed. At least one scenario was completed by 238 respondents. For all but one scenario, over 65% of respondents agreed that the identified concepts portrayed were sufficient for an informed decision; the exome scenario had the lowest agreement (58%). Qualitative analysis of the open-ended comments showed no consistently mentioned concepts to add or remove. The level of agreement with the example scenarios suggests that the minimum critical educational components for pre-test informed consent proposed in our prior work is a reasonable starting place for targeted pre-test discussions. This may be helpful in providing consistency to the clinical practice of both genetics and non-genetics providers, meeting patients' informational needs, tailoring consent for psychosocial support, and in future guideline development.

The Essential Need for Trust When Transmission Risk Cannot Be Eliminated in HIV-Remission Trials.

Analytic treatment interruption (ATI) is scientifically necessary in HIV-remission ("cure") studies to test the effects of new interventions. However, stopping antiretroviral treatment poses risks to research participants and their sexual partners. Ethical debate about whether and how to conduct such studies has largely centered on designing risk-mitigation strategies and identifying the responsibilities of research stakeholders. In this paper, we argue that because the possibility of HIV transmission from research participants to partners during ATI cannot practicably be eliminated-that is, it is ineliminable-the successful conduct of such trials ultimately depends on relationships of trust and trustworthiness. We describe our experiences with conducting and studying HIV-remission trials with ATI in Thailand to examine the strengths, complexities, and limitations of the risk-mitigation and responsibility approaches and to explore ways in which the building of trust-and trustworthiness-may help enhance the scientific, practical, and ethical dimensions of these trials.

Misunderstood terms and concepts identified through user testing of educational materials for fragile X premutation: "Not weak or fragile?"

Complicated genetic mechanisms and unpredictable health risks associated with the FMR1 premutation can result in challenges for patient education when the diagnosis is made in a newborn. From October 15, 2018, to December 10, 2021, North Carolina parents could obtain FMR1 premutation results about their newborns through a voluntary expanded newborn screening research study. The study provided confirmatory testing, parental testing, and genetic counseling. We developed web-based educational materials to augment information about fragile X premutation conveyed by a genetic counselor. Many genetics education materials are developed for the lay population. However, relatively little research is published on how well individuals understand these materials. We conducted three rounds of iterative user testing interviews to help refine web-based educational materials that support understanding and self-paced learning. The participants included 25 parents with a 2-year college degree or less and without a child identified with fragile X syndrome, premutation, or gray-zone allele. Content analysis of interview transcripts resulted in iterative changes and ultimately saturation of findings. Across all rounds of interviews, there were two terms that were commonly misunderstood (fragile and carrier) and two terms that elicited initial misconceptions that were overcome by participants. Many also had difficulty understanding the relationship between fragile X premutation and fragile X syndrome as well as appreciating the implications of having a "fragile X gene." Website layout, formatting, and graphics also influenced comprehension. Despite iterative changes to the content, certain issues with understandability persisted. The findings support the need for user testing to identify misconceptions that may interfere with understanding and using genetic information. Here, we describe a process used to develop and refine evidence-based, understandable parental resources on fragile X premutation. Additionally, we provide recommendations to address ongoing educational challenges and discuss the potential impact of bias on the part of expert content developers.

A Mixed-Method Study Exploring Patient-Experienced and Caregiver-Reported Benefits and Side Effects of Corticosteroid Use in Duchenne Muscular Dystrophy.

BACKGROUND: Corticosteroids are recommended to all people with Duchenne as standard of care; patient experience data is important to guide corticosteroid decision making and as a comparator for new treatment options. OBJECTIVE: This study assesses patient and caregiver-reported benefits and side effects from corticosteroids to treat Duchenne muscular dystrophy, their importance, and satisfaction. METHODS: Using one-on-one interviews (n = 28) and an online survey (n = 236), parents and adults with Duchenne reported corticosteroid benefits and side effects rated as both experienced and important. RESULTS: Benefits to breathing, heart function, arm strength, slowing progression of weakness, and getting around were rated as particularly important, regardless of ambulatory status. Important side effects included increased fracture risk, unwanted weight gain, and diabetes/prediabetes. Parents rated behavior issues and adults rated delayed puberty as having high importance. Being ambulatory was independently associated with reporting more net benefit (p = 0.02). For side effects, parent scores were significantly higher than adult score (p = 0.02). Corticosteroid type was not significant. Participants were, overall, satisfied with corticosteroids (means ranging from 6.2 to 7.7 on a scale of 0-10), with no significant differences based on corticosteroid type. CONCLUSIONS: Overall, most participants were satisfied with the use of corticosteroids. While a range of side effects were rated as important and relatively common, individuals using corticosteroids and their caregivers indicate that benefits outweigh the side effects. Qualitative data indicate that high acceptability is influenced by lack of treatment alternatives. Patient experience data on use of corticosteroids in Duchenne may be relevant to drug development, regulatory assessment of new treatments, and to families making decisions about corticosteroid use.

Development of a novel shared decision making aid for primary immunodeficiency diseases.

Aim: To describe development of a shared decision making (SDM) aid in treating primary immunodeficiency diseases (PID) with immunoglobulin replacement therapy (IGRT). Materials & methods: Expert engagement and qualitative formative research informed development. IGRT administration features were prioritized using object-case best-worst scaling (BWS) methodology. The aid was assessed by US adults self-reporting PID and revised following interviews/mock treatment-choice discussions with immunologists. Results: Patients participating in interviews (n = 19) and mock treatment-choice discussions (n = 5) deemed the aid useful/accessible and supported the utility of BWS, with content and BWS exercises refined following participant feedback. Conclusion: Formative research led to an improved SDM aid/BWS exercise, and illustrated how the aid may improve treatment decision making. The aid may help less-experienced patients and facilitate efficient SDM.

Shared decision making and developing a decision aid Shared decision making happens when patients and doctors work together to choose treatment options based on a patient's concerns, preferences, goals and values, as well as medical information. The aim of this project was to develop a decision aid to help patients with primary immunodeficiency diseases (PID), in which part of the body's immune system is missing or doesn't function correctly. This will allow patients to better understand and communicate with the healthcare team on their preferences about immunoglobulin treatments, which fight infection by boosting antibody (protein) levels in the blood. The authors talked to experts and reviewed existing information to decide what treatment features the aid should consider. Patients with PID then tested the aid, and changes were made based on their feedback. Doctors specializing in treating PID also provided their feedback. The final aid was judged to be helpful and easy to use by the participants. With further research, this aid could be used to help inexperienced patients better understand what immunoglobulin treatment features are most important to them, and support shared decision-making between patients and their doctors.

Reporting Individual-Level Research Results from Neurocognitive and Psychological Research in People Living with HIV: Lessons from Dementia Research.

PURPOSE OF REVIEW: There are growing expectations for the return of individual-level research results (RoR), which promotes autonomy and potential clinical and personal benefits. There are ethical and practical challenges, however, that may be exacerbated in research that assesses neurocognitive and psychological outcomes, including HIV-associated neurocognitive disorder (HAND). This paper reviews central concepts for RoR and recent empirical and conceptual articles from Alzheimer's disorder (AD) as a model for HIV. RECENT FINDINGS: Data from AD studies indicate high participant interest and low risk of harm from RoR, though additional research is needed. Investigators report a range of benefits, potential risks, and feasibility concerns. Standardized, evidence-based approaches are needed for RoR. For HIV research, we recommend a default position of offering RoR for cognitive and psychological outcomes. Investigators should justify decisions not to return results after assessing the potential value and feasibility of RoR. Longitudinal research is needed for feasible and evidence-based best practices.

Adaptation of the WOMAC for Use in a Patient Preference Study.

OBJECTIVES: To adapt a patient-reported outcome (PRO) measure, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), into efficacy attributes for a discrete choice experiment (DCE) survey designed to quantify the relative importance of endpoints commonly used in knee osteoarthritis (KOA) trials. METHODS: The adaptation comprised four steps: (1) selecting domains of interest; (2) determining presentation and framing of selected attributes; (3) determining attribute levels; and (4) developing choice tasks. This process involved input from multiple stakeholders, including regulators, health preference researchers, and patients. Pretesting was conducted to evaluate if patients comprehended the adapted survey attributes and could make trade-offs among them. RESULTS: The WOMAC pain and function domains were selected for adaption to two efficacy attributes. Two versions of the discrete choice experiment (DCE) instrument were created to compare efficacy using (1) total domain scores and (2) item scores for "walking on a flat surface." Both attributes were presented as improvement from baseline scores by levels of 0%, 30%, 50%, and 100%. Twenty-six participants were interviewed in a pretest of the instrument (average age 60 years; 58% female; 62% had KOA for ≥ 5 years). The participants found both versions of attributes meaningful and relevant for treatment decision-making. They demonstrated willingness and ability to tradeoff improvements in pain and function separately, though many perceived them as inter-related. CONCLUSIONS: This study adds to the growing literature regarding adapting PRO measures for patient preference studies. Such adaptation is important for designing a preference study that can incorporate a clinical trial's outcomes with PRO endpoints.

Use of a web-based portal to return normal individual research results in Early Check: Exploring user behaviors and attitudes.

Early Check is a voluntary, large-scale expanded newborn screening study in North Carolina that uses a self-directed web-based portal for return of normal individual research results (IRR). Little is known about participant perspectives in using web-based portals to receive IRR. This study explored user attitudes and behaviors within the Early Check portal using three methods: (1) a feedback survey available to the consenting parent of participating infants (typically mothers), (2) semi-structured interviews conducted with a subset of parents, and (3) Google Analytics. During an approximate 3-year period, 17 936 newborns received normal IRR and there were 27 812 visits to the portal. Most surveyed parents reported viewing their baby's results (86%, 1410/1639). Parents largely found the portal easy to use to get results, and helpful in understanding the results. However, 10% of parents said it was difficult to find enough information to understand their baby's results. In Early Check, providing normal IRR via the portal made a large-scale study practical, and was highly rated by most users. Return of normal IRR may be particularly amenable to web-based portals, as the consequences to participants from not viewing results are modest, and the interpretation of a normal result is relatively straightforward.

Sources of variation in estimates of Duchenne and Becker muscular dystrophy prevalence in the United States.

BACKGROUND: Direct estimates of rare disease prevalence from public health surveillance may only be available in a few catchment areas. Understanding variation among observed prevalence can inform estimates of prevalence in other locations. The Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) conducts population-based surveillance of major muscular dystrophies in selected areas of the United States. We identified sources of variation in prevalence estimates of Duchenne and Becker muscular dystrophy (DBMD) within MD STARnet from published literature and a survey of MD STARnet investigators, then developed a logic model of the relationships between the sources of variation and estimated prevalence. RESULTS: The 17 identified sources of variability fell into four categories: (1) inherent in surveillance systems, (2) particular to rare diseases, (3) particular to medical-records-based surveillance, and (4) resulting from extrapolation. For the sources of uncertainty measured by MD STARnet, we estimated each source's contribution to the total variance in DBMD prevalence. Based on the logic model we fit a multivariable Poisson regression model to 96 age-site-race/ethnicity strata. Age accounted for 74% of the variation between strata, surveillance site for 6%, race/ethnicity for 3%, and 17% remained unexplained. CONCLUSION: Variation in estimates derived from a non-random sample of states or counties may not be explained by demographic differences alone. Applying these estimates to other populations requires caution.

Corrigendum to 'Decision making for invasive and non-invasive optional procedures within an acute HIV research cohort in Bangkok,' [Contemporary Clinical Trials Communication (2023)101054].

[This corrects the article DOI: 10.1016/j.conctc.2022.101054.].

Decision making for invasive and non-invasive optional procedures within an acute HIV research cohort in Bangkok.

Clinical research regularly includes required, nontherapeutic procedures to answer research questions. Optional procedures usually offer minimal or no personal benefit and may involve harms and burdens. Members from the Bangkok SEARCH010/RV254 HIV research cohort of individuals acutely HIV-infected are recruited to six optional procedures varying in invasiveness: leukapheresis, genital secretions collection, lumbar puncture, brain MRI/MRS/DTI, colon biopsy, and lymph node biopsy. We surveyed cohort members about their first recruitment for each procedure to examine factors associated with decision making and attitudes about compensation. 406 members (68%) completed the survey. Reported procedure participation ranged from 71% (MRI) to 27% (lymph node biopsy). Respondents underwent 0-6 procedure types (median 3). Ordinal regression indicated that lower perceived HIV impact and HIV remission trial participation were associated with more procedures completed. Reports of decision difficulty varied, and feeling pressured by research staff was low overall. Notably, those who declined procedures and those who underwent more invasive procedures reported greater decision difficulty and perceived pressure. Most respondents felt compensation amounts were appropriate, although opinions differed by procedure, and for some procedures, between people who agreed and declined. There is limited literature regarding consent to and attitudes about optional research procedures. Researchers must consider how to best support voluntary decisions for procedures with little personal benefit, particularly in lower-income or marginalized populations. In this longitudinal research cohort, perceived pressure to participate may be a concern, although our finding of variation in participation rates corresponding to invasiveness is reassuring. Data from different research contexts would provide important comparators.